Process for the production of



United States PROCESS FOR THE PRODUCTION OF PYRlDYL-GLYCOLS Wilhelm Mathes and Walter Sauermilch, Ludwigshafen (Rhine), Germany, assignors to Dr. F. Raschig G.m.b.H. Chemische Fabrik, Ludwigshafen (Rhine), Germany No Drawing. Filed May 23, 1958, Ser. No. 737,203 Claims priority, application Germany May 31, 1957 2 Claims. (Cl. 2 60-288) wherein R=H and CH and R =H, an aromatic, heterocyclic or aliphatic radical.

The decarboxylation reaction can be carried out simply by heating a mixture of the reactants, for example, at temperatures between 50 C. and 100 C., preferably between 75 C. and 85 C., until evolution of CO ceases. As the decarboxylation reaction involves evolution of a gas, namely, CO it can be promoted by use of subatmospheric pressures.

Preferably stoichiometric proportions of the reactants are employed.

The following examples will serve to illustrate several embodiments of the invention:

Example 1 1.53 g. 1 mol) of a-pyridyl-glycolic acid was mixed With 1.07 g. i mol) of pyridine aldehyde-(2) and the mixture was heated on a steam bath until the evolution of CO ceased. The resulting tough dark mass crystallized upon cooling off and grinding. The crude reaction product was dissolved in boiling water and the solution treated with active carbon and filtered hot. Upon cooling, bispyridyl-(2)-glycol of a melting point of 156 C. crystallized out in the form of colorless crystals.

ExampleZ 1.52 g. mol) of tx-pyridyl glycolic acid was mixed with 1 cc. of 30% formaldehyde. The mixture was heated on a steam bath until the evolution of CO ceased. After cooling the reaction product with ice water the mono-pyridyl-(2)-g1ycol crystallized out in colorless crystals. After recrystallization from di-isopropyl-ether, it had a melting point of 98 C.

Example 3 1.53 g. 4 mol) of ot-pyridyl-glycolic acid was mixed with 1.48 g. (M mol) of water free chloral and heated on a steam bath with stirring until evolution of CO subsided. The dark brown reaction mass was boiled up several times, each time with 10 cc. of Water. The resulting hot solution was decolorized with active carbon and filtered. Upon cooling, about 1.8 g. of colorless crystals of pyridyl-(Z)-trichloromethyl-glycol having a melting point of 120 C. were obtained.

Example 4 6.7 g. 4 mol) of pyridyl-Z-hydroxy propionic acid were mixed with 6.3 g. mol) of quinoline-aldehyde- (2). The mixture was heated with stirring upon a steam bath (about 15 minutes) until evolution of CO ceased. After the product had cooled andstood overnight, about 25 cc. of methanol were added to the cloudy pasty reaction product and the mixture thoroughly stirred, whereupon a White precipitate of crystalline flocks separated out. The precipitate was filtered off on a suction filter and washed with methanol. 3 g. of the crude product of l-(pyridyl-Z)-l-methyl-2-(quinolyl- 2)-ethylene glycol-1.2 were obtained which were recrystallized from pyridine by precipitation with di-isopropyl ether. The recrystallized product had a melting point of 209-210 C. with decomposition.

Example 6 2)-1-methyl-2-(quinolyl-4) ethylene glycol 1.2 were obtained as colorless crystals with a melting point of 186- 187 C.

Example 7 5 g. mol) of pyridyl-Z-hydroxy propionic acid and 3.2 g. A mol) of freshly d stilled benzaldehyde were subjected to thermal decarboxylation as in Example 5. The reaction product was acidified with HCl and heated on a water bath until it had concentrated to a syrupy consistency. The syrup was placed in a desiccator over calcium chloride and after standing therein the hydrochloride of the glycol crystallized out. The crystals were purified by dissolving in Warm 1:1 acetone-ethanol mixture and filtering. Di-isopropyl ether was added to the filtered solution whereupon the hydrochloride of the glycol separated out in oily form. After several hours standing the oil solidified to crystals. 2.9 g. of l-(pyridyl-Z)-l-methyl-2-(phenyl)-ethyler1e glycol-1.2 of a melting point of 1l9-l21 C. were obtained.

Example 8 3.3 g. mol) of pyridyl-4hydroxy prop'onic acd and 2.2 g. mol) of benzaldehyde were decarboxylated as in Example 5. The reaction product was triturated with di-isopropyl ether and the crystalline glycol which flocked out was suction filtered. 4 g. of moist suction filtered crude product, 1-(pyridyl-4)-lmethyl-Z-phenyl-ethylene glycol 1.2 of a melting pont of 119-l32 C. were obtained. It was recrystallized from water and the recrystallized product had a melting point of l49.5-l5l C. Because of its hygroscopic characteristics it was converted to its hydrochloride, the melt ing point of which was 179-l81 C.

' 3 Example 9 Analogously 3.3 g. (2/1()() mol) of pyridyl-4-hydroxy 'propionic acid were heated together with 2.94- g. (25

mol) of water free chloral until evolution of CO ceased. The reaction product was triturated with di-isopropyl ether and the precipitated 1-(pyridyl-4)-l-methyl-Z-(trichloromethyD-ethylene glycol-1.2 filtered off on a suction filter. 2.1 g. of the product in the form of colorless crystals having a melting point of 189-190.5 C. were obtained. The product was converted to its hydrochloride, the melting point of which Was 206-207" C.

Example Example 11 Analogous to Example 10 about 2 g. of 1-(pyridyl-4)- lfmethyl-2-(pyridyl-3)-ethylene glycol 1.2 were obtained in the form of colorless crystals employing pyridine aldehyde-3 instead of pyridine aldehyde-4 and pyridyl- 4-hydroxy propionic acid instead of pyridyl-Z-hydroxy propionic acid. The product had a melting point of 188.5 C.

The pyridyl glycol compounds produced according to the invention are useful starting materials for many varied synthesis. For example: They can be used as starting materials in the known Criegee-cleavage to produce pyridine aldehydes or respectively acetyl pyridines (see W. Mathes and W. Sauermilch, Chem. Ber. 84, 457 (1951), and Chem. Ber. 85, 1009 (1952)). Also, according to Daniloff and Danilova, Chem. Ber. 59, 1041 (1926), one can obtain the correspondingly substituted acetaldehydes from substituted glycols.

4 We claim: 1. A process for the production of a pyridyl-glycol of the following formula:

ti IL H OH OH wherein R is selected from the group consisting of H and methyl radicals and R is selected from the group consisting of H, phenyl, pyridyl, quinolyl and alkyl which comprises heating a pyridyl glycolic acid' of the formula wherein R has the same significance as above in admixture with an aldehyde of the formula wherein R has the same significance as above to a temperature between C. and 100 C. to effect decarboxylation of said pyridyl glycolic acid in the presence of said aldehyde.

2. The process of claim 1 in which said decarboxylation is effected at temperatures between C. and

References Cited in the file of this patent UNITED STATES PATENTS Cislak Apr. 24, 1956 OTHER REFERENCES 

1. A PROCESS FOR THE PRODUCTION OF A PYRIDYL-GLYCOL OF THE FOLLOWING FORMULA: 